Butylated hydroxyanisole (
BHA), a synthetic
antioxidant is commonly used as a preservative in food and
pharmaceutical agents. Despite the assumed low toxicity of
BHA, it exerts a variety of effects on tissues and cell functions. In this study, the authors investigated the effects of
BHA on the growth inhibition and death of HeLa
cervical cancer cells. Dose-dependent inhibition of cell growth was observed with an IC(50) of approximately 150 μM
BHA at 24 h. In addition, this agent-induced apoptosis, which was accompanied by the loss of mitochondrial membrane potential (ΔΨ(m)) and
caspase activation.
Caspase-3 and -8 inhibitors markedly rescued HeLa cells from
BHA-induced cell death. In addition,
BHA decreased intracellular ROS levels in HeLa cells whereas it increased O(2)(∙-) levels among ROS. The number of
glutathione (GSH)-depleted cells was increased in 150 μM
BHA-treated cells, which was attenuated by
caspase inhibitors. In conclusion,
BHA inhibited the growth of HeLa cells via caspase-dependent apoptosis, which seemed to be related to increase in GSH depletion and O(2)(∙-) level.